Heretofore, various cyclic compounds have been proposed as the compounds useful for asthma and the like. For example, xanthine derivatives such as theophylline and β2-agonists such as salbutamol, steroids, antiallergic drugs and the like are known.
Further, various tricyclic condensed heterocyclic compounds are proposed.
Examples of such prior arts are mentioned below.
Yakugaku Zasshi, 87, (2), 198-201 (1967) discloses three dihydrodibenz[b,f]oxepin derivatives as the synthetic intermediates of a natural product but no pharmacological action and the like relating to these compounds are described.
U.S. Pat. No. 4,104,280 describes that tricyclc condensed heterocyclic compounds containing an oxygen atom or a sulfur atom as the heterocylic atom and a substituent of —CHRCOOH or —CHRCOOCH3(wherein R is a hydrogen atom or a methyl group) on the benzene ring are useful as anti-inflammatory drugs and relaxants.
European Patent Publication No. 0 011 067 A1 suggests that triclyclic condensed heterocyclic compounds containing a sulfur atom as the heterocyclic atom and —(CH2)n-A (wherein n is 0 to 4; and A is a heterocyclic residue) as one substituent on the benzene ring are effective for asthma, allergy and the like.
British Patent No. 2,016,466 describes that triclyclic condensed heterocyclic compounds containing an oxygen atom or a sulfur atom as the heterocyclic atom and —CH2COR (wherein R is OH, NH2, a C1-5 alkyl group or the like) as one substituent on the benzene ring are useful as anti-inflammatory drugs.
German Patent No. 32 03065 discloses that certain types of triclyclic condensed heterocyclic compounds containing an oxygen atom or a sulfur atom as the heterocyclic atom and various substituents on the benzene ring have pharmacological actions such as analgesia, sedation, antidepression, antispastic action.
European Patent Publication No. 0 003 893 discloses that triclyclic condensed heterocyclic compounds containing oxygen or sulfur as the heterocyclic atom and having —CHR2COOR3 (wherein R2 is a hydrogen atom or a methyl group; and R3 is a hydrogen atom or —CH2CH2OCH2CH2OH) as one substituent on the benzene ring have pharmacological actions such as anti-inflammation, analgesia and pyretolysis.
German Patent No. 1,302,590 describes tricyclic condensed heterocyclic compounds containing sulfur as the hetero atom and having various substituents on the benzene ring.
U.S. Pat. No. 4,104,280 teaches that 3-hydroxymethyl-benzo[b,f]thiepin containing a sulfur atom as the heterocyclic atom and its derivatives are used in the treatment of allergic diseases such as allergic asthma.
Br. J. Pharmac., 82, 389-395 (1984) describes 2-hydroxy-methyl-dibenzo[b,f]thiepin-5,5-dioxide which is an antagonist of prostanoids contractile for lung smooth muscles.
Japanese Pharm. Soc. Bull., 94, 299-307 (1989) suggests that 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid possibly becomes a clinically useful substance as an anti-inflammatory, analgesic and antipyretic drug since it only has a slight effect on circulatory organs and the autonomic nervous system when a considerably large amount is used.
WO Publication 96/10021 describes antioxidative tricylic condensed heterocyclic compounds containing oxygen or sulfur as the heterocyclic atom and having various' substitutents on the benzene ring.
WO Publication 96/25927 describes glutamic receptor blockers and cerebral function improving drugs containing oxygen or sulfur as the heterocyclic atom and having various substitutents on the benzene ring.
WO Publication 97/25985 describes tracheal smooth muscle relaxants having compounds containing oxygen or sulfur as the heterocyclic atom and having various substituents on the benzene ring as the effective component.
J. Org. Chem., 61, 5818-5822 (1996) and Collection Czechoslov. Chem. Commum., 43, 309 (1978) describe the synthesis of dibenzoxepins and dibenzothiepins.
Terahedron, 40, 4245-4252 (1984) and Phytochemistry, 31, (3) 1068-1070 (1992) describe dibenzoxepin derivatives derived from a natural substance.
Chem. Pharm. Bull., 23, (10) 2223-2231 (1975) and Chem. Pharm. Bull., 26, (10) 3058-3070 (1978) describe the synthetic methods of dibenzothiepin derivatives and the antiemetic action of these compounds.
J. Chem. Soc. Perkin Trans. 1, 3291-3294 (1991) and J. Med. Chem., 26, 1131-1137 (1983) describe the synthetic methods of dibenzoxepin and dibenzothiepin derivatives and the anti-estrogenic action of these compounds.
As stated above, heretofore, various tricyclic condensed heterocyclic compounds have been disclosed, but they cannot be said to be sufficient in respect of therapeutic effect, prolonged action, safety (in terms of preventing side effects) when used as therapeutic drugs for airway disorders such as bronchial asthma, acute or chronic bronchitis, pulmonary emphysema and upper esophagitis and the like and lung diseases, allergic diseases, chronic inflammation and the like. Thus, the development of novel compounds having a broad range of pharmacological actions including an airway smooth muscle relaxing action, an inhibition of airway hypersensitivity and an inhibition of infiltration of inflammatory cells into the airway and, at the same time, high safety (reduced side effects) is demanded.